The goals of this investigation are two-fold. First, we propose to characterize by specific immunocytochemical, radioimmunoassay and functional techniques a unique in vitro model which would permit the study of canine pancreatic polypeptide (PP) secretion from isolated dog pancreatic F cells. This methodology involves enzymatic dispersion of pancreatic endocrine and exocrine cells with subsequent specific aggregation of the endocrine cells into spherical, islet-like (pseudoislet) structures capable of withstanding repetitive static and perifusion incubations. Secondly, we propose to initiate in vitro secretion studies utilizing this model to evaluate: 1) a variety of stimulatory and inhibitory agents known to alter PP release in vivo. 2) the dynamic nature of PP secretion, 3) the role of ions in the release process, 4) the interrelationships of PP secretion with the release of insulin and glucagon, and 5) the involvement of cyclic nucleotides in the release process of PP. The primary goal is to elucidate the factors and mechanisms controlling PP secretion at the molecular level.